Discordant Protein and mRNA Expression in Lung Adenocarcinomas

The relationship between gene expression measured at the mRNA level and the corresponding protein level is not well characterized in human cancer. In this study, we compared mRNA and protein expression for a cohort of genes in the same lung adenocarcinomas. The abundance of 165 protein spots representing 98 individual genes was analyzed in 76 lung adenocarcinomas and nine non-neoplastic lung tissues using two-dimensional polyacrylamide gel electrophoresis. Specific polypeptides were identified using matrix-assisted laser desorption/ionization mass spectrometry. For the same 85 samples, mRNA levels were determined using oligonucleotide microarrays, allowing a comparative analysis of mRNA and protein expression among the 165 protein spots. Twenty-eight of the 165 protein spots (17%) or 21 of 98 genes (21.4%) had a statistically significant correlation between protein and mRNA expression (r > 0.2445; p 0.2445; p 0.2445; p 0.2445; p 0.2445; p A analysis of separate of proteins with levels of abundance than than or than also showed a of correlation between mRNA and protein expression among the and of 165 total protein (r = and determine the 21 genes protein a significant correlation between the protein and mRNA expression among all samples in this relationship tumor the were for stage I = and stage III = lung adenocarcinomas The number of non-neoplastic lung samples = was insufficient for a separate correlation analysis of this of the protein spots one of protein for a given The of genes not in the correlation between stage I and stage III tumors indicating a relationship between the mRNA and protein and however, were found to significant differences in the correlation between stage I and stage III lung adenocarcinomas. For and the in the correlation coefficient was because of a in protein expression in stage III tumors. For and the from a in expression of this protein in stage III tumors. little is the mechanisms the complex patterns of protein abundance and post-translational in tumors. Most the regulation of protein translation have focused on one or protein A. L. D. G. J.A. J.B. Jr., D.E. in the human cell of the 1996; Scholar). M. C. M. T. P. J. N. expression monitoring transcription and translation using DNA microarrays and 2000; Scholar) found a correlation between and protein levels among well proteins using a proteomic and of cancer. By the mRNA and protein expression levels within the same tumor samples, we found that of the protein spots genes) a statistically significant correlation between mRNA and proteins appear to a of gene and in protein modification, cell and that expression of this subset of 165 proteins is likely to be at the transcriptional level in these tissues. The of the protein isoforms, however, not with mRNA and their expression is by also a subset of proteins that demonstrated a correlation with the mRNA expression for demonstrated a correlation with mRNA expression may on the mRNA or the protein or the of that are not understood or in individual protein of the same gene to on 2D-PAGE gels and new new and new 1998; Scholar). the of all possible for each protein has not been characterized this may influence the correlation analyses performed in this study. is because of of the 2D-PAGE and mass spectrometry S.P. G.L. Y. Y. Aebersold R. of two-dimensional gel analysis Natl. Acad. Sci. U. S. A. 2000; Scholar, 2D or not gel Opin. 2001; Scholar). between mRNA and protein that have been may also be because of in the same in the mechanisms of protein translation among cells or as measured in S. D. P. N. M. protein at a level in human lung tumor cell Scholar). In this study, we 165 protein spots identified in lung adenocarcinomas. protein representing the of at protein of protein representing were to have a statistically significant correlation between their protein and mRNA expression, that the levels of these proteins the transcription of the corresponding in were found among the individual of a given For of the isoforms, showed a statistically significant correlation between the protein and mRNA expression The of relationship for the one however, that individual protein of the same gene can be is not and likely post-translational mechanisms that can influence abundance in tissues and cancer. In to the analyses of the correlation of mRNA/protein within the same tumor samples, we also the relationship between mRNA and the corresponding protein abundance across all 165 protein spots in the lung A protein and mRNA average for each gene was using all 85 lung tissues a of normalized average protein and mRNA The correlation coefficient using this average data was and for the protein spots that showed a statistically significant correlation between individual mRNA and proteins, the correlation was only that it is not possible to protein expression levels on average mRNA abundance in lung cancer is also by previous from and L. J. A of mRNA and protein in human Scholar), 19 genes in human and by S.P. Y. Aebersold R. Correlation between protein and mRNA abundance in Scholar), genes in studies found a of correlation between mRNA and protein expression average or levels were A correlation was the most proteins were in S.P. Y. Aebersold R. Correlation between protein and mRNA abundance in Scholar), that the level of protein abundance may be a that may influence the correlation between mRNA and In the present study, a of protein values among 165 protein spots in lung adenocarcinomas was and the correlation also varied from −0.467 to 0.442. A between the of each protein and the correlation coefficient using all 85 tissue samples not a relationship between the protein abundance and the correlation (r = p > analysis of of protein abundance also to a correlation between mRNA and protein in to a relationship between mRNA/protein correlation coefficient and protein abundance in human lung adenocarcinomas was not The of this that the level of protein abundance in lung adenocarcinomas is with the corresponding levels of mRNA in of the total 165 protein spots was than the to by was and that a transcriptional likely the abundance of these proteins in lung adenocarcinomas. also that the expression of individual of the same protein may or may not with the indicating that separate and likely post-translational mechanisms for the regulation of abundance. mechanisms may also for the differences in the correlation between stage I and stage III indicating that protein tumor studies in lung adenocarcinomas the relationship between the expression of individual protein and of these such as the of and or The potential to identify protein with in lung adenocarcinomas be of and to understanding of the regulation of gene by and post-translational A. D. C. and for in this study.